Inherited Type-1 renal tubular acidosis with short stature: a rare case report from Nepal

Renal tubular acidosis (RTA) refers to a group of disorders of multiple etiology characterised by a hyperchloremic, normal anion-gap metabolic acidosis caused by different defects affecting several mechanisms of urinary acidification: an impaired secretion of protons by collecting duct in distal hypokalemic RTA (type 1), impaired resorption of bicarbonate in proximal RTA (type 2), a mixed proximal and distal defect in RTA type 3 and an impaired ammoniagenesis due to an absolute or functional hypoaldosteronism in distal hyperkalemic RTA (type 4). Etiology is heterogeneous and ranges from primitive genetic forms to secondary RTA within a multi-system disorder such as autoimmune disease, paraproteinemia and calcium-phosphate disorders. Drug-induced RTA has been increasingly reported over the last decade due to widespread use of some molecules (e.g. antiviral and oncologic agents, inhibitors of renin-angiotensin system). The diagnosis of RTA is based on assessment of serum and urine anion-gap, whereas differe...

Metabolic Acidosis and Hyponatremia in a Patient With Metastatic Melanoma

Pathological fracture in Sjögren's syndrome due to distal renal tubular acidosis.

ObjectiveTo describe the clinical presentation and management of a critically ill dog with profound renal tubular acidosis (RTA) with proximal and distal renal tubular dysfunction.Case SummaryA 3‐year‐old neutered female Border Terrier was presented with frequent regurgitation resulting from acute pancreatitis with severe ileus. Venous acid–base analysis and complete urinalysis confirmed the presence of normal anion gap metabolic acidosis with inappropriately alkaline urine (pH 8), consistent with distal RTA. Urinalysis, urine amino acids, and urinary fractional excretion of electrolytes revealed glycosuria (with normoglycemia), aminoaciduria, and increased fractional excretion of sodium, calcium, and phosphate consistent with generalized proximal renal tubulopathy or Fanconi syndrome. The dog responded well to supportive care and alkaline therapy and made a complete recovery.New or Unique Information ProvidedTo the authors’ knowledge, this is the first description of RTA with proximal and distal renal tubular dysfunction in the veterinary literature. Furthermore, the authors hypothesize that the transient RTA was a manifestation of acute kidney injury secondary to acute pancreatitis, the first report of this in the literature.

Renal tubular acidosis (RTA) is a condition where there is a defect in renal tubular excretion of hydrogen ion (H+) or reabsorption of bicarbonate (HCO3−) or both. RTA is of four types: type 1 (distal RTA), type 2 (proximal RTA), type 3 (mixed type 1 and type 2), and type 4 (hyperkalemic RTA). Distal RTA (dRTA) may be inherited or acquired and is caused by impaired H+ ion secretion, leading to impair urinary acidification, resulting in hyperchloremic normal anion gap metabolic acidosis. The inherited (hereditary) form is the most common form of dRTA in children. The hereditary form of dRTA is diagnosed by genetic testing. dRTA due to homozygous pathogenic variations in the WRD72 (tryptophan–aspartate repeat domain 72) gene have also been linked to amelogenesis imperfecta (AI). Dental anomaly associated with dRTA is a rare presentation. This case report represents AI with dRTA associated with a novel mutation in the WDR72 gene.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy Type 1 (APECED) is a rare autosomal recessive disorder predisposing to early development of chronic mucosal candidiasis and progressive development of various endocrinopathies, such as Addison's disease, Primary Hypoparathyroidism, and Type 1 Diabetes (T1D). Few cases described in literature regarding renal involvement in this disorder, with most common manifestation being tubulo-interstitial nephritis, however, there is limited evidence regarding presentation of APECED with hypokalemia due to concomitant Type I Renal Tubular Acidosis (RTA). Case of a 47-year-old female with past medical history of APECED Type 1 (consisting of hypoparathyroidism, adrenal insufficiency, and chronic mucocutaneos candidiasis), T1DM on honeymoon, hypothyroidism, and nephrolithiasis presenting to the emergency department complaining of bilateral upper and lower extremity weakness of one week in evolution, but worsening on day of admission. Denies associated constitutional symptoms. Strong positive first-degree relative history for autoimmune diseases. Physical examination: 2/5 strength in all four extremities, deep tendon reflexes grossly intact, no gross sensory or motor deficits. Patient on oral steroid therapy for her Addison's, calcitriol supplementation for hypoparathyroidism, and potassium chloride supplementation since a prior hypokalemic episode 17 years ago. Laboratory workup results remarkable for sodium: 140 mmol/L (N: 135-144 mmol/L), chloride: 110 mmol/L (N: 95-105 mmol/L), potassium: 2. 0 mmol/L (N: 3.4-4.5 mmol/L), central bicarbonate: 18mmol/L (N: 23-31 mmol / L), anion gap: 12 (N: 10-12), glycosylated hemoglobin: 5.2% (N: 4.7-6.2%) and anti-glutamic acid decarboxylase antibodies >25,000 U/mL (N: <5 U/mL). Adrenal insufficiency was ruled out by laboratory findings, but she had normal anion gap metabolic acidosis (NAGMA) and hypokalemia. Urinalysis was negative for urinary tract infection but with pH: 7. 0 (N: 4.5-8. 0). Urine spots, measured to find the cause of her NAGMA, showed urine sodium: 92 mmol/L, urine potassium: 10 mmol/L, urine chloride: 90 mmol/L, and urine anion gap of 12 mEq/L, which is positive and suggests low urinary NH4+, consistent with Type I (Distal) RTA as the main etiology. Patient started on IV potassium replacement, which increased potassium to 3.8 mmol/L, and improved acidotic state, with central bicarbonate of 29mmol/L, and overall symptoms. Patient was discharged home with alkali therapy (Sodium citrate) for Type I (Distal) RTA. RTA is an underrecognized condition that may be inherited or acquired. Diagnosis is difficult but can be verified with a thoughtful workup. RTA should be considered for any patient with otherwise unexplained hyperchloremic metabolic acidosis and may be the presenting manifestation of autoimmune diseases. Regular renal monitoring for any APECED patient should be performed. We present this case as evidence for the coexistence of several different immune-mediated diseases in the clinical context of APECED with an unusual concomitant Type I (Distal) RTA, where there is few documented evidence of association with this disorder. Presentation: No date and time listed

Renal tubular acidosis (RTA) is a tubulopathy characterized by metabolic acidosis with normal anion gap secondary to abnormalities of renal acidification. RTA can be classified into four main subtypes: distal RTA, proximal RTA, combined proximal and distal RTA, and hyperkalemic RTA. Distal RTA (type 1) is caused by the defect of H(+) secretion in the distal tubules and is characterized by the inability to acidify the urine below pH 5.5 during systemic acidemia. Proximal RTA (type 2) is caused by an impairment of bicarbonate reabsorption in the proximal tubules and characterized by a decreased renal bicarbonate threshold. Combined proximal and distal RTA (type 3) secondary to a reduction in tubular reclamation of bicarbonate and an inability to acidify the urine in the face of severe acidemia. Hyperkalemic RTA (type 4) may occur as a result of aldosterone deficiency or tubular insensitivity to aldosterone. Clinicians should be alert to the presence of RTA in patients with an unexplained normal anion gap acidosis, hypokalemia, recurrent nephrolithiasis and nephrocalcinosis. The mainstay of treatment of RTA remains alkali replacement.

Distal renal tubular acidosis (dRTA) is an uncommon disorder marked by defective hydrogen ion excretion in the distal nephron, leading to hyperchloremic metabolic acidosis, persistently alkaline urine, and hypokalemia. Chronic, untreated dRTA in children often presents with growth failure, refractory rickets, and nephrocalcinosis, yet is frequently misdiagnosed. We report a 13-year-old girl with severe stunting, bone pain, proximal muscle weakness, and polyuria for several years. Examination revealed significant short stature, malnutrition, widened wrists, a protuberant abdomen, and genu valgum. X-rays demonstrated classical rachitic changes. Biochemical investigations showed severe hypokalemia (1.3 mEq/L) and metabolic acidosis (pH 7.22, HCO3- 7.6 mmol/L) with an inappropriately alkaline urine pH of 6.6. Imaging confirmed medullary nephrocalcinosis. A diagnosis of idiopathic distal renal tubular acidosis (RTA) was made. She was treated with oral alkali and potassium supplements. Over three months, acidosis improved (HCO3- 18 mmol/L), potassium normalized (3.2 mEq/L), and X-rays showed healing of rickets. Significant catch-up growth was noted, with a 10 cm height gain and 5 kg weight gain at six months. This case highlights the importance of considering dRTA in children with unexplained growth failure or rickets unresponsive to standard therapy. The classic triad - normal anion gap metabolic acidosis, hypokalemia, and alkaline urine - should prompt evaluation for dRTA. The treatment response with affordable alkali therapy is also highlighted, resulting in miraculous improvement in the patient.

Our patient initially presented with lupus nephritis and hyperkalaemia, with a normal anion gap and hyperchloraemic metabolic acidosis. A wide range of conditions have to be taken into account in the differential diagnosis for hyperkalaemia. Based on our patient’s laboratory findings, acute renal failure, drugs, blood transfusion and hemolysis were ruled out. Persistent hyperkalaemia and normal anion gap metabolic acidosis led us to suspect the presence of Type 4 RTA. This is included in the general classification of RTA as its cardinal feature is hyperkalaemia with a mild (normal anion gap) metabolic acidosis and normal measured urinary acidification [1]. Unlike distal RTA, in which proton secretion is defective, causing high urine pH, the main defect in Type 4 RTA is transport abnormality of the distal tubule, which is secondary to aldosterone deficiency, resistance or inhibition. The primary effect of aldosterone on the collecting duct is to stimulate sodium reabsorption and potassium secretion in principle cells, which results in an increase in the negative electrical potential of the lumen, promoting proton secretion. Aldosterone also directly affects the alpha intercalated cells to promote proton secretion by upregulating the expression of the proton ATPase as well as carbonic anhydrase. Thus, patients that are aldosterone deficient or resistant to aldosterone have increased sodium excretion [1, 2]. Our patient also had mildly increased of sodium excretion. The preferred method to estimate potassium excretion by the distal tubule is the TTKG. Our patient’s TTKGwas 5 in the presence of hyperkalaemia (normal >10), which indicates a defect in potassium secretion. A low TTKG is associated with aldosterone deficiency or resistance. The renin activity was 2.3 (5–27.8) pg/mL and the aldosterone level was 10 (13–340) pg/ L in the presence of high plasma levels of potassium. She appeared to have two distinct disorders, namely, renin– aldosterone deficiency or hyperkalaemic distal RTA. Her urine pH was 5.5 when the blood pH was 7.3, and the HCO was 16.8 mEq/L, which are suggestive of hyporeninaemic hypoaldosteronism (Type 4 RTA). Type IV RTA is the most common form of renal tubular acidosis and occurs in various disorders (Table 1). The most common causes of HH include diabetic nephropathy, tubulointerstitial disease and, in particular, interstitial nephritis associated with non-steroidal anti-inflammatory drugs (NSAIDs). Other causes in which hypoaldosteronism is present but not matched by hyporeninism include adrenal destruction (whether surgical, malignant or hemorrhagic), This article refers to the article that can be found at doi:10.1007/ s00467-2011-2040-5

Disclosure: J.U. Borlagdan: None. P. Dela Peña: None. B.R. Balanquit: None. J.L. Manuel: None.Distal renal tubular acidosis (dRTA) is a rare inherited disorder characterized by the nephron’s failure to acidify urine, leading to normal anion-gap metabolic acidosis. When left uncorrected, chronic acidosis promotes bone mineral resorption, resulting in significant skeletal complications. This report presents two cases of Filipino male patients with intractable hypokalemia, normal anion-gap metabolic acidosis with a positive urine anion gap, and hypocalcemia, ultimately leading to growth failure, progressive height loss, and skeletal deformities.Case 1 describes a 20-year-old male with persistent hypokalemia, growth stunting, bone deformities, and delayed puberty since childhood. Despite correction of serum potassium and bicarbonate levels with potassium citrate and calcium/vitamin D supplementation, he exhibited continued growth delay and bone deformities at follow-up. Case 2 involves a 36-year-old male with chronic hypokalemia, progressive height loss of 79% (from 165 cm to 131 cm), disabling bone pain, scoliosis, and contracture deformities. His history revealed years of inadequate treatment with potassium chloride alone. Diagnostic findings confirmed dRTA, and management with potassium citrate was initiated.dRTA results from defects in acid excretion, either due to primary genetic mutations or secondary conditions such as autoimmune diseases or nephrotoxins. The chronic acidotic state shifts bone metabolism toward resorption through increased RANKL activity and suppressed osteoblastic function, predisposing patients to osteomalacia, fractures, and growth failure. Unlike other renal osteodystrophies, dRTA-induced bone disease is acidosis-dependent and preventable with early intervention.Both cases highlight the importance of timely diagnosis and proper management, particularly in suspected hereditary dRTA. Alkali therapy with potassium citrate is the cornerstone of treatment, effectively reversing metabolic acidosis and preventing nephrolithiasis. However, long-term mismanagement, as seen in these patients, can lead to irreversible skeletal damage. Early intervention is crucial to prevent debilitating complications, underscoring the necessity for increased awareness and appropriate treatment strategies. Keywords: distal renal tubular acidosis, growth failure, skeletal sequelae, metabolic acidosis, hypokalemiaPresentation: Saturday, July 12, 2025

1. James C.M. Chan, MD* 2. Jon I. Scheinman, MD† 3. Karl S. Roth, MD* 1. 2. *From the Department of Pediatrics and the Department of Biochemistry Molecular Biophysics, Virginia Commonwealth University, Richmond, VA 3. 4. †Department of Pediatrics at the University of Kansas, Kansas City, KS. Objectives After completing this article, readers should be able to: 1. Describe the important presenting characteristics of renal tubular acidosis (RTA). 2. Delineate the mechanisms of the growth failure commonly encountered in RTA. 3. Characterize the various types of primary RTA. 4. Describe diagnostic tests and treatment modalities available for RTA. 5. Delineate the conditions giving rise to secondary distal and proximal RTA. A 2-month-old Caucasian female presented for failure to thrive. She was born at 33 weeks’ gestation via primary cesarean section for pregnancy-induced hypertension to a 38-year-old G1P0 mother. Her birthweight was 1,430 g, making her small for gestational age. Apgar scores were 7 and 9 at 1 and 5 minutes, respectively. Newborn metabolic screen results were negative. At 3 weeks of age, with good oral intake of formula, alternating with breastfeeding, the infant was discharged from the hospital. The infant’s paternal grandfather died at age 61 from bronchitis and heavy smoking. The 60-year-old paternal grandmother was healthy and well. There was no family member of short stature. The 38-year-old mother (162.6 cm) and the 46-year-old father (175.3 cm) both were in good health. The maternal grandfather, age 72, had a history of renal stones. The 67-year-old maternal grandmother (157.5 cm) had a history of gallstones. No one in the family was on dialysis or had kidney diseases except for the maternal grandfather’s renal stones. At 2 months of age, the infant had persistent failure to thrive and a 1-day history of irritability and vomiting and was readmitted for diagnostic evaluation. Serum bicarbonate level was 12 mEq/L (12 mmol/L), and she was tachypneic, with a respiratory rate of 60 breaths/min and intercostal retraction. Her height was 48.5 cm (<5th percentile) and her weight was 3.45 kg (<5th percentile). Blood pressure was 81/48 mm Hg. She was alert and calm, with normal skin turgor. …

Distal renal tubular acidosis (dRTA) is characterized by the inability to excrete acid in the renal collecting ducts resulting in inappropriately alkaline urine and hyperchloremic (normal anion gap) metabolic acidosis in the context of a normal (or near-normal) glomerular filtration rate. Inborn dRTA can be due to autosomal dominant or recessive gene defects. Clinical symptoms vary from mild acidosis, incidental detection of kidney stones or renal tract calcification to severe findings such as failure to thrive, severe metabolic acidosis, and nephrocalcinosis. The majority of patients with recessive dRTA present with sensorineural hearing loss (SNHL). Few cases with abnormal widening of the vestibular aqueduct have been described with dRTA. Mutations in three different genes have been identified, namely SLC4A1, ATP6V1B1, and ATP6V0A4. Patients with mutations in the ATP6V1B1 proton pump subunit develop dRTA and in most of the cases sensorineural hearing loss early in childhood. We present two patients from two different and non-consanguineous families with dRTA and SNHL. Direct sequencing of the ATP6V1B1 gene revealed that one patient harbors two homozygous mutations and the other one is a compound heterozygous. To our knowledge, this is the first case in the literature describing homozygosity in the same dRTA gene on both alleles.

Type 3 renal tubular acidosis is a pathological condition characterized by the simultaneous occurrence of distal renal tubular acidosis, which causes urinary acidification disorders, and proximal renal tubular acidosis, which causes impaired reabsorption of bicarbonate ions. Type 3 renal tubular acidosis is considered rare. A 5-year-old boy was admitted to our hospital because of frequent vomiting, poor vitality, and fever. He was diagnosed with cyclic vomiting syndrome. Type 3 renal tubular acidosis was also diagnosed because of severe mixed metabolic acidosis with impaired urinary acidification, a low tubular phosphorus reabsorption rate with hypophosphatemia, low-molecular-weight proteinuria, pan-aminoaciduria, and glucosuria. Fluid infusion was performed. On the second day of hospitalization, the vomiting disappeared and the patient was able to eat and drink. He was discharged on the eighth day of hospitalization. The laboratory test abnormalities associated with the renal tubular acidosis gradually improved, and testing at discharge on the eighth day of admission showed no metabolic acidosis, hypophosphatemia, low-molecular-weight proteinuria, or glucosuria. These findings suggested that the type 3 renal tubular acidosis was transient. Severe metabolic acidosis was observed in this patient because of both normal anion gap metabolic acidosis due to type 3 renal tubular acidosis and anion gap metabolic acidosis due to cyclic vomiting syndrome. Although type 3 tubular acidosis is rare, the resultant metabolic acidosis worsens when combined with a disease that causes metabolic acidosis. Type 3 tubular acidosis should be ruled out when severe metabolic acidosis is present.

We report on four siblings (three males, one female) born to first cousin Arab parents with the constellation of distal renal tubular acidosis (RTA), small kidneys, nephrocalcinosis, neurobehavioral impairment, short stature, and distinctive facial features. They presented with early developmental delay with subsequent severe mental, behavioral and social impairment and autistic-like features. Their facial features are unique with prominent cheeks, well-defined philtrum, large bulbous nose, V-shaped upper lip border, full lower lip, open mouth with protruded tongue, and pits on the ear lobule. All had proteinuria, hypercalciuria, hypercalcemia, and normal anion-gap metabolic acidosis. Renal ultrasound examinations revealed small kidneys, with varying degrees of hyperechogenicity and nephrocalcinosis. Additional findings included dilated ventricles and cerebral demyelination on brain imaging studies. Other than distal RTA, common causes of nephrocalcinosis were excluded. The constellation of features in this family currently likely represents a possibly new autosomal recessive syndrome providing further evidence of heterogeneity of nephrocalcinosis syndromes.

IntroductionBile cast nephropathy (BCN) is a rare and often overlooked cause of acute kidney injury (AKI), usually seen in the context of severe hyperbilirubinemia. It results from the deposition of bile pigments and bile casts in renal tubules, specifically distal and collector tubules, leading to obstruction and direct tubular toxicity.Case descriptionWe describe the case of 49-year-old male who presented with severe jaundice and oliguric AKI. With the gradual resolution of liver dysfunction, the patient’s kidney function also improved. However, during the recovery phase, the patient developed persistent hypokalaemia and normal anion gap metabolic acidosis. Further work-up was consistent with distal renal tubular acidosis (dRTA).DiscussionWhile BCN is being increasingly recognized in patients with cholestatic liver diseases, complications arising during the recovery phase – particularly acid-base disturbances like dRTA – are rarely reported. In this case, the onset of dRTA during renal recovery may reflect delayed or selective tubular healing after bile-induced injury. This case highlights the importance of continued monitoring for renal tubular defects even after apparent improvement in glomerular function.ConclusionThis case emphasizes the need to consider dRTA as a potential complication in patients recovering from BCN. Close follow-up of electrolyte and acid-base parameters is advised during renal recovery, especially in the presence of persistent hypokalaemia.LEARNING POINTSBile cast nephropathy (BCN) is an under-recognized cause of acute kidney injury (AKI) in patients with severe hyperbilirubinemia and should be considered in the differential diagnosis of AKI in jaundiced patients.Distal renal tubular acidosis (dRTA) can emerge during the recovery phase of BCN-related AKI, possibly due to tubular dysfunction from bile-induced injury, highlighting the need for close metabolic monitoring after renal recovery.The co-occurrence of BCN and dRTA emphasizes the importance of serial electrolyte assessments and acid-base evaluation in jaundiced patients with AKI, even after apparent improvement in renal function.